We propose to continue studies of the pathogenesis of glomerular injury, with two major projects. First, we will continue our studies of the role of fixed glomerular negative charges in normal and abnormal glomerular permselectivity. Using a model of acute reversible proteinuria induced by infusion of the polycation hexadimethrine, we will observe the effect of hexadimethrine: a) on glomerular structure as judged by electron microscopy using hydrophylic and hydrophobic embedding media, b) on renal hemodynamics as measured by inulin and PAH clearances, c) on permselectivity as measured by fractional clearance of labeled model proteins, modified to be electroneutral or to have net negative charges, and d) on the trapping of oligomers of human immunoglobulin by the glomerulus. Second, we will continue our studies of the role of cell mediated immunity in glomerular injury associated with immune complex nephritis. We will determine the effect on acute serum sickness nephritis in rabbits of treatment with antibodies to macrophages and to T-lymphocytes given after immunization to BSA, but before onset of overt renal injury. We will also study in vitro the reactivity of circulating T-lymphocytes from these animals to the immunizing antigen, in order to correlate the state of cell mediated immunity with the appearance of overt disease.